The purpose of this research is to investigate the sequence of electron carriers associated with cyanide-resistant respiration in isolated mitochondria. Cyanide-resistant respiration occurs in a wide range of plants and, in some animals including pathogenic protozoa of the genus Trypanosoma (sleeping sickness). There is conflicting information in the literature concerning 1) the role of ubiquinone and a specific iron-sulfur protein, center S-3 of succinate dehydrogenase, in cyanide-resistant respiration and 2) the presence of iron at the site of inhibition by substituted hydroxamic acids; specific inhibitors of cyanide-resistant electron transfer. Two inhibitors, dibromothymoquinone and carboxin are being used to characterize the roles of ubiquinone and center S-3 respectively in cyanide-resistant electron transfer. Work includes rapid kinetic experiments designed to elucidate the site(s) of action of the two inhibitors on the mitochondrial electron transfer chain. A model system using ubiquinone-incorporated liposomes will be used to study the mechanism of interaction of dibromothymoquinone with the ubiquinone pool. Finally, a series of 12 hydroxamic acids will be used to ascertain what chemical feature(s) are necessary to inhibit cyanide-resistant electron transfer. These latter studies should help clarify the question of the involvement of iron in cyanide-resistant electron transfer.